CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma
CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma
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DOI：
10.1007/s13277-015-4172-x
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Ouyang, Nengtai
中科院分区：
文献类型：
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作者：
Lin, Zeyu;Li, Wenbin;Ouyang, Nengtai
趋化因子配体18（CCL 18）与肝细胞癌（HCC）转移有关。在这里，我们证明了一种新的机制，通过CCL 18增强细胞迁移，侵袭和上皮间质转化（EMT）在肝癌。(1)使用免疫组织化学，我们分析了149例HCC组织标本中PITPNM 3的表达，PITPNM 3是一种与CCL 18信号相关的分子。结果表明，PITPNM 3的表达与肿瘤的转移和分化密切相关;（2）体外实验表明，CCL 18可增强PITPNM 3（+）肝癌细胞的迁移、侵袭和EMT，但对PITPNM 3（-）肝癌细胞无明显作用。通过短干扰RNA（siRNA）沉默PITPNM 3抑制CCL 18诱导的细胞迁移、侵袭和EMT;（3）在PITPNM 3（（+））HCC细胞中，CCL 18诱导的细胞迁移、侵袭和EMT伴随IKK和IKB α的磷酸化以及p65核转位，但在用siRNA沉默PITPNM 3的细胞中不存在，暗示NF-κ B信号传导的激活涉及CCL 18/PITPNM 3的作用。这些结果表明，CCL 18通过PITPNM 3的表达和NF-κ B信号通路的激活增强HCC细胞的迁移、侵袭和EMT。
Chemokine ligand 18 (CCL18) has been associated with hepatocellular carcinoma (HCC) metastasis. Here, we demonstrated a novel mechanism through which CCL18 enhances cell migration, invasion, and epithelial-mesenchymal transition (EMT) in HCC. (1) Using immunohistochemistry, we analyzed the expression of PITPNM3, a molecule that correlated with CCL18 signaling, in 149 HCC tissue specimens. The results showed that PITPNM3 expression is highly associated with tumor metastasis and differentiation; (2) in vitro experiments showed that CCL18 enhances cell migration, invasion, and EMT in PITPNM3((+)) HCC cells but not in PITPNM3((-)) cells. Silencing of PITPNM3 by short interfering RNA (siRNA) inhibited the induction of cell migration, invasion, and EMT by CCL18; (3) Cell migration, invasion, and EMT induced by CCL18 accompanied with the phosphorylation of IKK and IKB alpha as well as p65 nuclear translocation in PITPNM3((+)) HCC cells, but not in the cells that PITPNM3 is silenced with siRNA, implying that the activation of NF-kappa B signaling is involved in the action of CCL18/PITPNM3. These results suggest that CCL18 enhances HCC cell migration, invasion, and EMT through the expression of PITPNM3 and the activation of the NF-kappa B signaling pathway.